FUNCTION OF THE PVN IN HEART FAILURE--ROLE OF NITRIC OXIDE AND GABA

心力衰竭（HF）患者和所有HF动物模型均表现出交感神经激活增加。这种异常增加了心衰期间死亡的风险。这些异常背后的主要机制尚不清楚。我们最近获得的数据表明，室旁核（PVN），一个已知的接收来自心脏的传入信息并改变交感神经流出的中心位置，可能有助于在HF状态下升高的神经-体液驱动。此外，PVN内一氧化氮（NO）和γ -氨基丁酸（GABA）机制的改变可能参与了这种交感神经兴奋。这一建议提出了PVN内NO和GABA机制被破坏导致心力衰竭交感驱动增加的假设。我们建议：首先，确定PVN内是否没有机制导致HF大鼠交感神经活动增加；其次，确定PVN内的GABA机制是否有助于心衰大鼠交感神经活动的增加；第三，确定HF大鼠PVN内NO和GABA机制的相互作用是否发生改变；第四，确定运动训练是否能改善HF大鼠PVN内NO和GABA机制的改变。预计PVN内的No和GABA机制有助于心衰期间常见的交感神经激活。这些结果应该为交感神经兴奋的中枢机制提供重要的新信息，特别是PVN内的NO和GABA系统参与了NF状态下交感神经激活的增加。了解迄今尚未研究的中枢机制在心衰状态交感神经激活增加中的作用。了解交感神经驱动增强中的中枢机制的作用（迄今尚未研究）将提高我们治疗心衰及其心血管并发症的能力。

Patients with heart failure (HF) and all animal models of HF exhibit an increased sympathetic neural activation. This abnormality increases the risk of mortality during HF. The central mechanisms which underlie these abnormalities are poorly understood. We have recently obtained data which suggests that the paraventricular nucleus (PVN), a central sit known to receive afferent information from the heart and to alter sympathetic outflow, may contribute to the elevated neuro-humoral drive during the HF state. Furthermore, altered nitric oxide (NO) and gamma-amino butyric acid (GABA) mechanisms within the PVN may be involved in this sympatho-excitation. This proposal sets the hypothesis that disrupted NO and GABA mechanisms within the PVN contribute to the increased sympathetic drive in heart failure. We propose to: first, determine if No mechanisms within the PVN contribute to the increased sympathetic nerve activity in rats with HF; second, determine if GABA mechanisms within the PVN contribute to the increased sympathetic nerve activity in rats with HF; third, determine if there is altered interaction of NO and GABA mechanisms within the PVN in rats with HF; and fourth, determine if exercise training improves the altered NO and GABA mechanisms within the PVN in rats with HF. It is anticipated that No and GABA mechanisms within the PVN contribute to the sympathetic neural activation commonly observed during HF. The results should provide significant new information regarding central mechanisms of sympatho-excitation, specifically involvement of the NO and GABA systems within the PVN, in the increased sympathetic neural activation in the NF state. Understanding the role of central mechanisms not studied to date, in the increased sympathetic neural activation in the HF state. Understanding the role of central mechanisms, not studied to date, in the increased sympathetic neural drive would enhance our ability to treat HF condition and its cardiovascular complications.